| Human Immunodeficiency Virus (HIV) is a retrovirus of the lentivirus genus and is the etiologic agent of acquired immunodeficiency syndrome (AIDS). UNAIDS estimated that in 2003, world wide there were over 3 million AIDS related deaths, 5 million new infections and currently over 40 million individuals infected with HIV. Further, due to logistical, social, financial and political issues, anti-retrovirul drug therapy is not a feasible option in developing countries. Production of an effective vaccine has the potential to control the HIV epidemic. This dissertation contains the results of experiments guided towards the development of an HIV vaccine. Chapter one is a literature review, which gives background for currently licensed human viral vaccines, how they work and how the knowledge of these vaccine methodologies apply to the development of a HIV vaccine. Additionally it gives information about models used to test HIV vaccine strategies and results of HIV vaccine strategies tested in the rhesus macaque model. Chapter two compares the virology and immunology after delivery of an attenuated viral vaccine (SHIV 89.6) as a plasmid DNA construct as opposed to a suspension of virions. Chapter three describes the protective efficacy and the identification of correlates of protection against pathogenic SIV challenge in proviral SHIV 89.6 plasmid DNA vaccinated animals. Chapter four describes the immunogenicity of a vaccine cocktail containing multiple non-replicating plasmid DNA constructs expressing multiple genes of SIV and the protective efficacy against pathogenic SIV challenge. Chapter five suggests future experiments to develop a better understanding of these two vaccine methodologies, as well as a better understanding of how HIV exposures could effect vaccine efficacy. |
